title: Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer.
abstract: BACKGROUND
  Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer.
  
  
  METHODS
  One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2 O2 -induced mutation rates of lung cancer cells with or without E6 expression.
  
  
  RESULTS
  Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P = .006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P = .012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2 O2 -induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells.
  
  
  CONCLUSIONS
  HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.
authors.affiliation: Department of Surgery, Tung' Taichung MetroHarbor Hospital, Taichung, Taiwan, Republic of China; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Min-Che
authors.initials: MC
authors.lastname: Tung
authors.forename: Heng-Hsiung
authors.initials: HH
authors.lastname: Wu
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Lee
authors.initials: L
authors.lastname: Wang
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Sauh-Der
authors.initials: SD
authors.lastname: Yeh
authors.forename: Tzu-Chin
authors.initials: TC
authors.lastname: Wu
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D016296:Mutagenesis; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D066246:ErbB Receptors; D003849:Deoxyguanosine
keywords: 8-dihydro-2&#38; prime;-deoxyguanosine; 8-oxo-7; epidermal growth factor receptor; human papillomavirus; lung cancer; mutation